HIV Vaccine

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  • 1 World Health Organization
    Global AIDS epidemic continues to grow
    GENEVA, 21 NOVEMBER 2006
    According to the latest figures published today in the UNAIDS/WHO 2006 AIDS Epidemic Update, an estimated 39.5 million people are living with HIV. There were 4.3 million new infections in 2006 with 2.8 million (65%) of these occurring in sub-Saharan Africa and important increases in Eastern Europe and Central Asia, where there are some indications that infection rates have risen by more than 50% since 2004. In 2006, 2.9 million people died of AIDS-related illnesses.
    2 Joint United Nations Programme on HIV/AIDS (UNAIDS) (December 2006). AIDS epidemic update (PDF). World Health Organization.
    3 IAVI (International AIDS Vaccine Initiative)
    and those currently living with the virus, in the past two decades more than 60 million people have been infected.
    HIV's spread shows no signs of slowing. There is an estimated 14,000 new infections daily, or nearly 600 infections every hour every day.More than 95% of new infections are occurring in developing countries. Best current projections suggest that tens of millions more people will become infected with HIV by the end of the decade, mostly in developing countries unless the world succeeds in mounting a drastically expanded, global prevention effort.
    *The Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization keep the latest statistics on the number of HIV/AIDS cases worldwide. From their December 2003 report:
  • The functionally important epitopes of the gp120 protein are masked by glycosylation, trimerisation and receptor-induced conformational changes making it difficult to block with neutralising antibodies. it is difficult for antibodies to bind to gp120; also, it can easily be shed from the virus' surface and captured by T-cells due to its loose binding with gp41
    Wikipedia AIDS vaccine article
    Based on its genetic sequence, HIV-1 has been grouped into different subtypes named alphabetically (subtypes A to K)
    AIAVI
    HIV has various clades that are clustered epidemiologically in geographic regions.
    perhaps no vaccine-elicited immune response is fully capable of eliminating or containing HIV replication.
    AIAVI
    50 years to develop an effective vaccine
    Hundred million dollars should be spent
    Many failure
    AVAC
  • Much progress has been made since 2000.
    The number of AIDS vaccine candidates in small-scale human trials has doubled since 2000. The number of countries and agencies involved has also grown. Currently, more than 30 candidate AIDS vaccines are being tested in small-scale human clinical trials, the majority of which began in the past seven years. These trials span 19 countries on six continents. The number of agencies working toward a vaccine has increased as well. Four pharmaceutical companies have vaccine candidates in trials, up from two in 2000.
    Developing countries, which in 2000 participated in vaccine research and development only marginally, are now helping lead the field in trials. In 2000, one African country, Uganda, was conducting an AIDS vaccine trial. Today, four African countries have small-scale trials underway, and five others are preparing for trials. As the number of small-scale trials in developing countries grows, so too does capacity to conduct these trials. Throughout Africa, Asia and Latin America, state-of-the-art clinics and laboratories, staffed by local physicians and technicians, exist where four years ago there were none. It is critical that developing countries conduct AIDS vaccine trials because the incidence of new HIV infections is among the highest in these areas. In addition, the subtypes of HIV circulating in developing countries are different from the subtype common in industrialized countries. Scientists do not yet know if or how subtype will impact a vaccineユs effectiveness.
    The first-ever large-scale AIDS vaccine trials were completed in 2003. To be fully evaluated for safety and effectiveness, a vaccine candidate must first be tested in small-scale trials, then tested in large-scale trials. In early 2003, a large-scale trial of VaxGenユs AIDSVAX candidate was completed in North America. Later in 2003, a second trial of AIDSVAX was completed in Thailand. Although both trials found the candidates to be ineffective, the trials themselves were major milestones. Before these trials were completed there were many that doubted that you could even logistically carry out this sort of research. The VaxGen trials demonstrated that it is possible to recruit thousands of volunteers for an AIDS vaccine trial and retain them over a three-year observation period.
  • This slide shows past, present and future sites for HIV vaccine trials. It is important to note that trials are being undertaken in the global north as well as the global south. It is important to test vaccines in multiple settings.
    There are two major HIV variants that are responsible for the global epidemic, HIV-1 and HIV-2. These two viruses are quite different, and a vaccine generated against one will not necessarily provide protection against the other. Therefore, when companies and researchers are designing vaccines, the strain that they use to derive the DNA and proteins is an important consideration. What offers protection from the dominant strain in the US may not offer protection in regions of Africa or in Asia.
  • whole-killed AIDS vaccine uses HIV that has been rendered incapable of replication, usually through chemical treatment. Such vaccines have proven useful in other viral diseases, and are potentially safer than live-attenuated virus vaccines, provided that complete inactivation is achieved in the manufactured product. The primary advantage of this approach is that all of the viral antigens are presented in a completely "native" form. Its primary disadvantage is the difficulty in maintaining this "native" configuration during the chemical inactivation required to render the product safe for humans. It is also difficult to make large quantities of this type of vaccine.
  • Live, attenuated virus vaccines mimic natural exposure while avoiding disease, in the expectation that immunologic memory and lifelong immunity will be induced, just as in youngsters who recover from the usual childhood infections. These vaccines effectively induce both humoral and cell-mediated immunity, and generally require only one or two immunizations, since the immune responses they induce are very durable. While most licensed vaccines in use today for other diseases are based on this concept, formidable safety concerns have limited research on live, attenuated HIV vaccines in humans.
  • LIVE VECTOR VACCINES Live recombinant vector vaccines are constructed by inserting HIV or SIV genes into live, infectious, but non-disease-causing viruses or bacteria such as vaccinia virus or Bacille Calmette-Guerin (BCG). These vaccines are produced by engineering viral or bacterial genomes to express the desired HIV antigen(s). Viral vectors can be constructed to contain one or more viral genes that cause infected cells to make the coded protein in native form. Recombinant viral vectors enter cells and allow the HIV or SIV proteins to be generated inside the cells; these proteins are then presented to the immune system in the same way that proteins from a virus-infected cell would be. As a result, vector-based vaccines induce both humoral and cellular immune responses. The antibody response to some live vector experimental vaccines can be substantially augmented by subsequent boost with recombinant subunit protein vaccines. In addition, some live vector vaccines may be capable of generating a mucosal immune response.
  • RECOMBINANT VIRAL SURFACE PROTEIN VACCINES HIV subunit vaccines use viral surface antigens, particularly gp120 and gp160, to evoke an immune response. Subunit vaccines consist of small protein or peptide portions of pathogenic virus. They can be made by genetically engineering bacteria, yeast, insect or mammalian cell cultures to produce protein subunit antigens.Envelope subunit and peptide approaches were among the earliest attempts to make an HIV vaccine, based on the premise that the envelope protein is a prominent, "visible", and important target which binds to cells and facilitates viral entry.
  • Naked DNA Vaccines DNA immunization uses the genes for viral antigens, rather than the antigens themselves, as the source of immunogen. In DNA immunization, the host is immunized by direct administration of viral genes; the genes are composed of DNA that encode for the antigen that would normally be produced by the cell infected with the virus. The vaccinee's cells take up the DNA and produce viral antigen by normal cellular mechanisms. The newly-formed antigen is then presented on the cell surface with host MHC class I and class II molecules where contact with immunocompetent cells evokes an immune response.
    18 trials in stage I are DNA types /25
    2/4 in stage I/II
    2 in stage II
  • PSEUDOVIRIONS Virus-like particles (VLP) take advantage of the fact that the immune system responds well to particulate antigens that are the size of viruses. The self-assembling core structures of many different viruses can be adapted by recombinant technology to contain or display one or more antigens of HIV (or SIV). Since these particles neither replicate nor contain the HIV genome, they cannot produce progeny virus and so avoid the formidable safety concerns associated with whole-inactivated and live-attenuated virus vaccines. "Pseudovirions" or genetically inactivated HIV, are a special kind of VLP. They are self-assembling, non- replicating, virus-sized structures that closely resemble the intact HIV virion.
  • An HIV vaccine may be totally successful in preventing infection, known as "sterilizing immunity." Sterilizing immunity may be possible in 100% of the population, or perhaps only in certain groups.
    With sterilizing immunity there would be no detectable HIV at any time and no risk transmission of HIV to others.
    An alternative HIV vaccine outcome would be Transient Infection. In this case HIV infection occurs, but the immune system is primed to detect and kill off infected cells. The disease process would not advance, and there would be no detectable HIV at later time points, such as 6-12 months after infection. The person may or may not seroconvert (become HIV+ by ELISA and Westrn blotting), and importantly, a person still may be able to transmit HIV to others during the window of transient infection.
    The third case would be Long-term controlled infection. In this setting there would be undetectable or very low viral load throughout life but no harmful drop in CD4 cells. Thus the person would not progress to AIDS, though seroconversion is likely. In this case transmission to others is possible, but because of the low viral load, diminished.
    The final outcome of an HIV vaccine would be the development of an altruistic vaccine. This type of vaccine would give little benefit to the vaccinated individual, but would help prevent transmission to others.
    The viral load in mucosal secretions would remain low so the vaccinated person may stay health for a longer period than if not vaccinated. HIV transmission would be prevented or greatly reduced.
  • Incidence
    Prevalence
    Placebo controlled double blinded trials
  • New adult HIV infections in low- and middle-income countries by year and vaccine scenario (The introduction of a vaccine at 2015 was chosen for illustrative purposes. A vaccine is not guaranteed by 2015.)
    IAVI (International AIDS Vaccine Initiative) Why the World Needs an AIDS Vaccine ? article
  • Researchers are taking clues from the ways the body naturally responds, or fails to respond, to HIV.
    For example, on average 10 years elapse from the time one is infected with HIV to when the virus has done enough damage to warrant AIDS diagnosis. This means that the immune system has some ability to control HIV, albeit temporarily, and the role of a vaccine will be to boost these defenses to where they can deliver a decisive blow. Additionally, there are rare individuals who exhibit an exceptional ability to live without ever becoming immunocomprimised, people termed long-term non-progressors, and analysis of what is different about their immune systems is yielding ideas for vaccines. For example, some female sex workers have remained HIV uninfected for years, despite repeated sex without condoms. Researchers are building and testing vaccines designed to stimulate cytotoxic t cells and other immune cells that are believed to be responsible for these womenユs upper hand against the virus.
    Experimental vaccines against SIV, a close cousin of HIV that infects monkeys, have been shown to prevent AIDS. Together, these findings support the scientific potential for a vaccine to prevent AIDS in humans.   Iavi
  • It has been 20 years since the first promise of a vaccine was uttered. What still needs to happen?
    significant new resources need to be devoted worldwide to AIDS vaccine research and development. In particular, new resources are needed for development of vaccines that will be applicable for developing countries. These funds must not be diverted from therapeutics or other prevention efforts.
    Governments need to commit the necessary resources to provide AIDS vaccines, when they are available, to all who need them without delay. This includes securing binding commitments for financing the purchase and delivery of vaccines for poor countries.
    There needs to be further involvement of industry in AIDS vaccine development, as most vaccine-making expertise and capacity reside there. Participants in human trials of vaccines must receive adequate support, as they are the unsung heroes of vaccine development.
    vaccine research and development needs to be part of a comprehensive strategy to fight the epidemic. The world must redouble its commitment to existing prevention programs, including education. And all who are living with HIV/AIDS deserve the best treatment possible, regardless of where they live or ability to pay.
    the public sector of all nations to work with private industry, international agencies and nongovernmental organizations to end the epidemic. Twenty years into the epidemic, AIDS remains a global emergency that demands an effective response. A preventive vaccine is the best hope to end AIDS for all time.
  • HIV Vaccine

    1. 1. 60 million people, infected since 1981 39.5 million people are living with HIV 4.3 million new infections in 2006 Over 28 million have died since 1981 Ten new infections occur every minute
    2. 2. Facts Special Features of HIV Human Immune System Response Ideal HIV Vaccine Current Achievements Prospective
    3. 3. FactsFacts  AIDS kills more people than any other infectious disease  Impact on economics  Unreliable pharmacotherapy  HIV is the best studied pathogen  Yet we don’t have any vaccine for it
    4. 4. Facts Special Features of HIV Human Immune System Response Ideal HIV Vaccine Current Achievements Prospective
    5. 5. Special Features of HIV  HIV is highly mutable  Genetically diverse population of viruses  Too variable epitopes of the viral envelope  Masking of gp120  High levels of viral replication Long latent period of infection
    6. 6. Special Features of HIV GP 120
    7. 7. Slide 7.37
    8. 8. Facts Special Features of HIV Human Immune System Response Current Achievements An Ideal HIV Vaccine Prospective
    9. 9. Human Immune System Response Humeral immunity
    10. 10. Human Immune System Response Cell-mediated immunity
    11. 11. Facts Special Features of HIV Human Immune System Response Current Achievements An Ideal HIV Vaccine Prospective
    12. 12. Current Achievements Since 2000 30 vaccine versions have been tried  Many clinical trials are ongoing in developing countries  Large scale AIDS vaccine trials could be conducted
    13. 13. Current Achievements
    14. 14. Live Attenuated Whole Killed Live Vector Re- combinant Proteins DNA Vaccines Pseudo virion Vaccine Types Current Achievements
    15. 15. Whole, Killed HIV  Not under study in primates  No useful immunity  Difficult to maintain viral configuration  Difficult to make large quantities
    16. 16. Live, Attenuated HIV Studied in non- human primates Has pathogenic potentiality
    17. 17. Live Vector Vaccines  Phase I and II trials  Inserting HIV or SIV genes into viruses or bacteria  Effective humoral and cellular immune responses
    18. 18. Recombinant Viral Protein Vaccines  Phase III  Uses viral surface antigens as immunogens  Uses genetically engineered bacteria, yeasts, insects or cell cultures
    19. 19. Naked DNA Vaccines  Stages I , I/II and II  Synthesizing antigens using host-cell’s machinery  Presented on the cell surface with host MHC class I and class II molecules
    20. 20. Pseudovirions Pre-clinical trials Virus-like particles Self-assembling, non- replicating, virus-sized structures
    21. 21. Facts Special Features of HIV Human Immune System Response Current Achievements An Ideal HIV Vaccine Prospective
    22. 22. An Ideal HIV VaccineAn Ideal HIV Vaccine Sterilizing Long-term controlled infection Transient Infection Altruistic vaccine
    23. 23. Epidemiological Aspect Individual Aspect An Ideal HIV VaccineAn Ideal HIV Vaccine
    24. 24. Efficacy  Protection from infection Sterilizing immunity  Protection from disease Reduction in set point viral loads Time after infection Viralload Ideal vaccine Peak Set point Sub optimal vaccine
    25. 25. Facts Special Features of HIV Human Immune System Response Current Stand An Ideal HIV Vaccine Prospective
    26. 26. Total New Infections Averted By An AIDS VaccineNewinfectionsinmillion Vaccine introduction Base Low scenario Medium scenario High scenario Total new infections averted by an AIDS vaccine between 2015-2030 30% efficacy 20% coverage 50% efficacy 30% coverage 70% efficacy 40% coverage 5.5 million 28 million 17 million 28 million
    27. 27. Is an AIDS vaccine really Preparable? Is an AIDS vaccine really Preparable? In 1984 researchers predicted that a vaccine was right around the corner…
    28. 28. INTERNATIONAL HEALTH SECURITY 2007 …..HIV/AIDS threatens the stability of entire regions and nations…. While there are major efforts under way to find a vaccine and to expand access to affordable treatments, much more still needs to be done…
    29. 29. What To Do Now?
    30. 30. Conclusions  The scale of HIV problem is huge  Humanity needs an effective vaccine to end the pandemic  Developing an HIV vaccine is a laborious task  HIV vaccines on different stages of trials are only partially effective  The best primary prevention up till now is : - Health education - Personal protection
    31. 31. Acknowledgments  Dr. Seyed Mohsen Mahmoodi  Dr. Abdel Hamid Elhawary  Mr. Mohammad Reza Rahimi  Dr. Rizwana Sheikh
    32. 32. THANKTHANK YOU!!!YOU!!! You Can Visit My Website: www.mahmoodi.org

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